A 2-part, Phase 1-2, open-label, parallel group, randomized study in patients with Castration-Resistant Prostate Cancer (CRPC) who are no longer responding to treatment with abiraterone and steroids. In Part A (Phase 1), patients will continue to receive the same doses of abiraterone and steroids they were receiving prior to study entry and will be randomized to receive 1 of 2 different treatment regimens of AT13387 in combination with abiraterone. Once the best regimen is established in Part A, based on safety and antitumor activity, patients will be randomized to the selected treatment regimen and dose of AT13387 in combination with abiraterone or AT13387 alone in Part B (Phase 2).

Part A: Safety and tolerability of the combination of AT13387 and abiraterone and to select the most promising treatment regimen in CRPC patients who are no longer responding to treatment with abiraterone alone. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Part B: Compare the antitumor activity (response rate per the Prostate Cancer Working Group 2 [PCWG2]) between single-agent AT13387 and combination of AT13387 plus abiraterone in patients who are no longer responding to treatment with abiraterone alone. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

AT13387 given as a 1-hr IV infusion at a starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle, in combination with abiraterone acetate 1000 mg by mouth (PO) daily (QD) and prednisone or prednisolone 5 mg PO twice daily.

Drug: AT13387

Regimen 1: AT13387, given as 1-hr intravenous infusion at starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle. Regimen 2: AT13387, given as 1-hr IV infusion at starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle.

Other Name: onalespib

Drug: abiraterone acetate

1000 mg PO daily.

Drug: Prednisone

5 mg PO twice daily.

Other Name: prednisolone

Experimental: Part A, Regimen 2

At13387 administered as a 1-hr IV infusion at a starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle, in combination with abiraterone acetate 1000 mg by mouth (PO) daily (QD) and prednisone or prednisolone 5 mg PO twice daily.

Drug: AT13387

Regimen 1: AT13387, given as 1-hr intravenous infusion at starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle. Regimen 2: AT13387, given as 1-hr IV infusion at starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle.

Other Name: onalespib

Drug: abiraterone acetate

1000 mg PO daily.

Drug: Prednisone

5 mg PO twice daily.

Other Name: prednisolone

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Male

Accepts Healthy Volunteers:

No

Criteria

Inclusion:

Must have prostate cancer

Have received prior castration by orchiectomy and/or hormone therapy

Males >18 years of age

Normal activity level for self care

Have been receiving abiraterone therapy with a steroid for ≥1 month

Have disease progression on abiraterone as defined by either PSA progression, radiographic or bone progression

Have adequate bone marrow, liver and kidney function

Must be willing to provide pre-existing tumor samples, if this material exists. If pre-existing samples are not available, a sample must be obtained during screening

Must be willing and able to provide written informed consent and comply with the protocol and study procedures

Have received chemotherapy within 4 weeks prior to receiving study drug

Prior prostate surgery or radiotherapy within 4 weeks from the first dose of study drug

Hypersensitivity to AT13387 or other components of the drug product

Treatment with any investigational drug within 4 weeks prior to the first dose of study drug

Severe systemic diseases or active uncontrolled infections

Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors

Abnormal heart function

Other cancer except for adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder cancer, or other cancer from which the subject has been disease-free for at least 3 years;

No known brain or CNS involvement

Unable to receive corticosteroids or history of pituitary or adrenal dysfunction

Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685268